Atrophy is one of the major age-related changes in the brain. The absence of brain atrophy in elderly individuals reflects deceleration in the process of biological aging. Moreover, results from human twin studies suggest a large genetic influence on the variance of human brain tissue volumes. To investigate the association of brain volumes with exceptional longevity, we tested whether middle-aged to elderly offspring of nonagenarian siblings have larger brain volumes than their spouses using magnetic resonance imaging. No differences in whole brain, gray matter and white matter volume were found. These brain volumes were associated with chronological age in offspring and control subjects (all P < 0.001). Left amygdalar volume of the offspring was larger (P = 0.03) compared with control subjects [mean volume offspring (cm3) (95% confidence interval, CI) = 1.39 (1.36-1.42), mean volume control subjects (cm3) (95% CI) = 1.32 (1.29-1.35)]. Association of left amygdalar volume with familial longevity was particularly pronounced when offspring with the oldest long-lived parent were compared with control subjects (P = 0.01). Amygdalar volumes were not associated with chronological age in both groups. Our findings suggest that the observed association of a larger left amygdalar volume with familial longevity is not caused by a relative preservation of the left amygdala during the course of aging but most likely a result of early development caused by a genetic familial trait.